Osteoporosis and related fractures are serious and costly public health problems that are projected to increase substantially as our elderly population grows. Women experience a higher incidence of all types of osteoporotic fractures. Although factors affecting retention of bone mass are of critical importance, those affecting peak bone mass acquisition at younger ages also impact upon later risk of osteoporotic fractures. Depo- medroxyprogesterone acetate (Depo-Provera, DMPA), an injectable derivative of progesterone, recently became the first injectable contraceptive to receive FDA approval for use in the US--an action likely to increase DMPA use both here and abroad. Preliminary evidence suggests that long-term users of DMPA have lower bone density than non-users. However, the issue has not received rigorous examination in large-scale epidemiologic studies. This research proposes to prospectively evaluate the effects of DMPA on the bone density of healthy pre-menopausal women. We propose to conduct a prospective epidemiologic study of the effects of initiation, ongoing use, and discontinuation of DMPA in 175 women who are receiving injections and a comparable group of 350 women who are not. The cohort will be selected from among women HMO enrollees between the ages of 18-39. A new outpatient automated database will be used to identify women receiving DMPA injections. The HMO membership file will be used to randomly select women who are not exposed to DMPA, frequency matching to the age and primary care clinic of exposed women. Eligible women who agree to participate will be followed for 24 to 36 months. The primary outcome, bone mineral density (BMD), will be evaluated by measurement of the hip, AP lumbar spine, and total body calcium using dual-energy X-ray absorptiometry. Following the baseline visit, BMD will be measured at 6- month intervals until the end of the study period. A secondary aim of the study will be to prospectively assess the effects of DMPA exposure on biochemical indices of bone metabolism. DMPA represents an effective, convenient and inexpensive contraceptive option for US women. Prompt evaluation of this potential effect of its use is essential, not only from the standpoint of acting to diminish the future burden of osteoporosis, but in order to assure this remains a viable contraceptive alternative. Moreover, if no effect on bone density is noted, one remaining safety issue for this product may be put to rest